The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
It has long been accepted that certain wavelengths of electromagnetic radiation, such as ultraviolet light, have the ability to affect biological and chemical structures. For example, the formation of thymine dimers under the influence of ultraviolet light is well known and has been utilized to sterilize surfaces by killing or inactivating a variety of pathogens. In the early 1900's efforts were made to incorporate exposure to ultraviolet light as a treatment modality for various diseases, including bacterial and viral infections. Procedures were typically extracorporeal; a volume of blood would be removed from a patient, irradiated to modify a patient's immune response and/or decrease the bacterial or viral load, and returned to the patient. Such efforts were hindered, however, by the sources of ultraviolet light available at the time. UV lamps of the time period did not operate reliably, produced inconsistent illumination, and generated large amounts of heat. The development of effective and reliable antibiotics that were easily administered resulted in a loss of interest in this therapeutic approach.
The increasing prevalence of antibiotic-resistant pathogens and the recognition of potential effectiveness for the treatment of noninfectious medical conditions has led to an increasing interest in the use of blood irradiation as a treatment modality. A variety of devices for improved extracorporeal irradiation of blood have been proposed. For example, International Patent Application Publication No. WO2006/128047 (to Petrie) and United States Patent Application Publication No. 2006/0157426 (to Petrie) disclose devices for the irradiation of volumes of blood taken from a patient using devices that expose blood ultraviolet light, and incorporate shutters that allow control of the degree of irradiation. Other extracorporeal devices have included mechanisms for mixing the volume of blood taken from the patient in order to improve exposure during the irradiation process. Both active agitation of blood (European Patent No. EP0951305B1, to Morris) and use of static mixers with plasma preparations (United States Patent Application Publication No. 2003/127,603, to Horowitz et al) have been disclosed. Approaches involving the removal and reinfusion of a specific volume of blood are, however, necessarily limited in their ability to irradiate large blood volumes from an individual. In addition, they expose the patient to the risk of reinfusion with treated blood from a different individual, through either mislabeling or human error. The extensive exposure of blood to non-biological surfaces also carries with it the risk of unwanted clotting and resulting embolisms. While this is, to some extent, preventable through the use of anticoagulants the use of such substances also carries substantial risk.
Approaches in which blood is removed, irradiated, and returned to the patient in a continuous fashion have been described (United States Patent Application Publication No. 2013/0101464 to Smyczynski). Similarly, United States Patent Application Publication No. 2004/0186407 (to Walker) teaches a semi-batch approach, in which from a patient is collected in a reservoir, irradiated with ultraviolet light while contained as a thin film, and then returned to the patient in a cyclical fashion. Such extracorporeal approaches, however, still necessarily involve the use of complex equipment, damage to blood cells and platelets through exposure to equipment surfaces, and formation of blood clots.
Alternative methods for the irradiation of blood have been proposed. For example, European Patent Application No. 2,179,767 A1, to Kokos and Jurinyi, discloses a device for irradiation of blood through the membranes of the patient's nasal mucosa. Various devices have also been developed that permit direct irradiation of blood or tissue within the vasculature or body cavity of a patient. For example, U.S. Pat. No. 4,693,556 (to McCaughan) describes placing an optical fiber equipped with an optical radiator into a body cavity. The use of multiple waveguides providing ultraviolet light to an implanted catheter for the purpose of reducing catheter-associated infections in described in U.S. Pat. No. 8,460,229 (to Dacey). It is not clear, however, how effective approaches are in irradiating blood.
Attempts have also been made to irradiate blood while it is within the vascular system. U.S. Pat. No. 5,505,725 (to Samson) and U.S. Pat. No. 6,908,460 (to DiStefano) describe devices that place a conventional optical fiber directly in a vein by inserting it through a hypodermic needle following venipuncture. Such approaches, however, fail to provide for the accidental breakage of the inserted optical fiber and the subsequent loss of efficient irradiation and release of the resulting fragments into circulation. Such breakage is a known issue with quartz or silica materials that are typically utilized in optical fibers, particularly when subjected to relatively sharp bends such as upon insertion into a vein. In addition, such optical fibers lack sufficient rigidity to remain in one position within a vein when subjected to the pulsatile flow of blood, and may collide with and damage the interior of the vein.
While ultraviolet light, which has a known germicidal effect, has been used by a number of investigators for irradiation of blood (as noted above), other wavelengths of light have also been considered. For example, United States Patent Application Publication No. 2004/0073278 (to Pachys) describes an implanted light sources for irradiation of body tissues that has selectable frequencies. U.S. Pat. No. 6,908,460 (to DiStefano) discusses alternating between ultraviolet and visible wavelengths during irradiation. Other investigators have suggested combining different wavelengths during irradiation, as discussed in U.S. Pat. No. 8,460,229 (to Dacey et al). The rationale for changing or combining frequencies of light during irradiation, however, is not clear in these.
These and all other extrinsic materials discussed herein are incorporated by reference in their entirety. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.
While certain devices and methods are known in the art to irradiate blood, all or almost all of them suffer from one or more disadvantages. Thus, there is still a need for simple device for the effective in vivo irradiation of blood.